The objective of the proposed research is to determine the physical chemical basis for the subunit interactions of certain well characterized enzymes and to delineate the regulatory role of subunit interactions in physiological situations. Hexokinase from yeast and mammalian sources and muscle aldolase will be studied to determine the relationship between ligand binding, conformational changes, and association-dissociation equilibria with an interpretation based upon the three dimensional structure of the enzymes. Reacting enzyme sedimentation, and allosteric properties of yeast hexokinase and erythrocyte hexokinase will be studied under varying conditions. Sedimentation equilibrium, conformational changes, and chemical modifications of yeast hexokinase and aldolase will be studied in order to determine the relationship between these properties. The physiological role of subunit interactions will be studied in yeast "ghosts", red cell "ghosts", with regulatory mutants of yeast hexokinase, and by the effect of 2,3-diphosphoglycerate on erythrocyte hexokinase in the presence of hemoglobin. These studies of the subunit interactions of hexokinase in vivo have implications for the understanding and control of diabetes and cancer. BIBLIOGRAPHIC REFERENCES: Cavalieri, S.J., Neet, K.E., and Goldthwait, D.A. (1976) Gene 5 Protein of Bacteriophage fd: A Dimer Which Interacts Coopratively with DNA. J. Mol. Biol. 102, 697-711. Cavalieri, S. J., Goldthwait, D.A. and Neet, K. E. (1976) The Isolation of a Dimer of Gene 8 Protein of Bacteriophage fd. J. Mol. Biol. 102, 713-722.